Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias.

Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Research Abstract Details 

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Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Abstract Text:

Barry London,Michael Michalec,Haider Mehdi,Xiaodong Zhu,Laurie Kerchner,Shamarendra Sanyal,Prakash C Viswanathan,Arnold E Pfahnl,Lijuan L Shang,Mohan Madhusudanan,Catherine J Baty,Stephen Lagana,Ryan Aleong,Rebecca Gutmann,Michael J Ackerman,Dennis M McNamara,Raul Weiss,Samuel C Dudley,Barry London,Michael Michalec,Haider Mehdi,Xiaodong Zhu,Laurie Kerchner,Shamarendra Sanyal,Prakash C Viswanathan,Arnold E Pfahnl,Lijuan L Shang,Mohan Madhusudanan,Catherine J Baty,Stephen Lagana,Ryan Aleong,Rebecca Gutmann,Michael J Ackerman,Dennis M McNamara,Raul Weiss,Samuel C Dudley,

BACKGROUND: Brugada syndrome is a rare, autosomal-dominant, male-predominant form of idiopathic ventricular fibrillation characterized by a right bundle-branch block and ST elevation in the right precordial leads of the surface ECG. Mutations in the cardiac Na+ channel SCN5A on chromosome 3p21 cause approximately 20% of the cases of Brugada syndrome; most mutations decrease inward Na+ current, some by preventing trafficking of the channels to the surface membrane. We previously used positional cloning to identify a new locus on chromosome 3p24 in a large family with Brugada syndrome and excluded SCN5A as a candidate gene. METHODS AND RESULTS: We used direct sequencing to identify a mutation (A280V) in a conserved amino acid of the glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) gene. The mutation was present in all affected individuals and absent in >500 control subjects. GPD1-L RNA and protein are abundant in the heart. Compared with wild-type GPD1-L, coexpression of A280V GPD1-L with SCN5A in HEK cells reduced inward Na+ currents by approximately 50% (P<0.005). Wild-type GPD1-L localized near the cell surface to a greater extent than A280V GPD1-L. Coexpression of A280V GPD1-L with SCN5A reduced SCN5A cell surface expression by 31+/-5% (P=0.01). CONCLUSIONS: GPD1-L is a novel gene that may affect trafficking of the cardiac Na+ channel to the cell surface. A GPD1-L mutation decreases SCN5A surface membrane expression, reduces inward Na+ current, and causes Brugada syndrome.

Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Publishing Authors By Initials

B London,M Michalec,H Mehdi,X Zhu,L Kerchner,S Sanyal,PC Viswanathan,AE Pfahnl,LL Shang,M Madhusudanan,CJ Baty,S Lagana,R Aleong,R Gutmann,MJ Ackerman,DM McNamara,R Weiss,SC Dudley,B London,M Michalec,H Mehdi,X Zhu,L Kerchner,S Sanyal,PC Viswanathan,AE Pfahnl,LL Shang,M Madhusudanan,CJ Baty,S Lagana,R Aleong,R Gutmann,MJ Ackerman,DM McNamara,R Weiss,SC Dudley,

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Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Circulation

VOLUME: 116

Page Numbers: 2260-8

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ISSN: 1524-4539

DAY: 29

MONTH: 10

YEAR: 2007

Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Information

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LANGUAGE: eng

NlmUniqueID: 147763

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Grant and Affiliation Information for Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias.

AFFILIATION: Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife S-572, 200 Lothrop St, Pittsburgh, PA 15213-2582, USA. londonb@upmc.edu

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL73753

ACRONYM: HL

MEDLINETA: Circulation

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